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PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription [Affymetrix]

ABSTRACT: PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription [Affymetrix]

PROVIDER: PRJNA493119 | ENA |

REPOSITORIES: ENA

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PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription [Affymetrix]

Project description:We demonstrate that PTEN interacts with the transcription machinery. Using ChIP-seq, we show that PTEN co-localizes with RNAPII and binds to chromatin in promoter and putative enhancer regions. We further show that loss of PTEN affects RNAPII occupancy in gene bodies and correlates with gene expression changes. Loss of PTEN also increased cells’ sensitivity to transcription inhibition via small molecules.

2019-04-03 | GSE120472 | GEO

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription.[RNA-seq and ChIP-seq]

2019-04-03 | GSE120439 | GEO

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription

Project description:PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription

| PRJNA493120 | ENA

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription.[RNA-seq and ChIP-seq]

Project description:PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription.[RNA-seq and ChIP-seq]

| PRJNA493122 | ENA

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription.

Project description:Regulation of RNA polymerase II (RNAPII)-mediated transcription controls cellular phenotypes such as cancer. Phosphatase and tensin homologue deleted on chromosome ten (PTEN), one of the most commonly altered tumor suppressors in cancer, affects transcription via its role in antagonizing the PI3K/AKT signaling pathway. Using co-immunoprecipitations and proximal ligation assays we provide evidence that PTEN interacts with AFF4, RNAPII, CDK9, cyclin T1, XPB and CDK7. Using ChIP-seq, we show that PTEN co-localizes with RNAPII and binds to chromatin in promoter and putative enhancer regions identified by histone modifications. Furthermore, we show that loss of PTEN affects RNAPII occupancy in gene bodies and further correlates with gene expression changes. Interestingly, PTEN binds to promoters and negatively regulates the expression of genes involved in transcription including AFF4 and POL2RA, which encodes a subunit of RNAPII. Loss of PTEN also increased cells' sensitivity to transcription inhibition via small molecules, which could provide a strategy to target PTEN-deficient cancers. Overall, our work describes a previously unappreciated role of nuclear PTEN, which by interacting with the transcription machinery in the context of chromatin exerts an additional layer of regulatory control on RNAPII-mediated transcription.

| S-EPMC6582409 | biostudies-literature

PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy [ChIP-seq]

Project description:Control of gene expression is one of the most complex yet continuous physiological processes impacting cellular homeostasis. RNA polymerase II (Pol II) transcription is tightly regulated at promoter-proximal regions by intricate dynamic processes including Pol II pausing, release into elongation, and premature termination. Here, we identify PTEN interacting with the Pol II transcription machinery and dephosphorylating Pol II C-terminal domain in vitro. PTEN alters the expression of hundreds of genes, and its restoration establishes Pol II promoter-proximal pausing in PTEN null cells. Furthermore, PTEN re-distributes genome-wide Pol II occupancy and possibly impacts Pol II pause duration, release, and elongation rate in order to enable precise gene regulation at genome-wide scale. Our observations demonstrate a direct and imperative role of PTEN in global transcriptional regulation.

2019-06-04 | GSE124657 | GEO

PTEN modulates gene transcription by redistributing genome-wide RNA polymerase II occupancy [RNA-seq]

2019-06-04 | GSE124658 | GEO

PTEN interacts with the transcription machinery on chromatin and regulates RNA polymerase II-mediated transcription

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-04-03 | GSE120478 | GEO

Nuclear PTEN safeguards pre-mRNA splicing to link Golgi apparatus for its tumor suppressive role

Project description:Dysregulation of pre-mRNA alternative splicing (AS) is closely associated with cancers. However, the relationships between the AS and classic oncogenes/tumor suppressors are largely unknown. Here we show that the deletion of tumor suppressor PTEN alters pre-mRNA splicing in its phosphatase-independent manner, and identify262 PTEN-regulated AS events in 293T cells by RNA sequencing, which are associated with significant worse outcome of cancer patients. Based on these findings, we report that nuclear PTEN interacts with the splicing machinery, spliceosome, to regulate its assembly and pre-mRNA splicing. Especially, the exon-2b exclusion of GOLGA2 contributes to PTEN knockdown-induced tumorigenesis by promoting dramatic Golgi extension and secretion, and PTEN depletion significantly sensitizes cancer cells to secretion inhibitors, Brefeldin A and Golgicide A. Given that many cancers lack PTEN expression, our results suggest that Golgi secretion inhibitors alone or in combination with PI3K/Akt kinase inhibitors may be therapeutically useful for PTEN-deficient cancers.

2018-10-18 | PXD009681 | Pride

Topoisomerase 3B Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing

Project description:Topoisomerase 3B Interacts with RNAi Machinery to Promote Heterochromatin Formation and Transcriptional Silencing

| PRJNA488415 | ENA